While even a single episode of depression is disabling and entails considerable economic loss and emotional suffering, recurrent depression represents a major public health problems. Effective treatments are available for the acute depressive episode but relatively few clinical trials have been conducted on the maintenance treatment or prevention of subsequent episodes. Until now maintenance treatment for recurrent unipolar depression has focused exclusively on the implementation of somatic therapies with only moderate success. It is time that an investigation of psychological treatment is applied to this problem. Over the next five years we intend to achieve the following major aims: (1) to determine whether long-term (3 years) formal psychotherapeutic treatment on a monthly basis is more efficacious in preventing recurrence than a medication clinic in which patients also are seen once a month; (2) to determine whether active drug treatment (imipramine) given in the medication clinic over the same time period (3 years); (3) to ascertain whether changes in selected biological, psychosocial, and clinical signs precede, or are associated with, a recurrence. Such assessments will also allow us to describe the phenomenology of recurrent depression using biological correlates of early warning signs (prodromata) of recurrence in patients with a well-established history of recurrent major depression.